Measurable residual disease study through three different methods can anticipate relapse and guide early interventions in childhood acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Measurable residual disease (MRD, previously named minimal residual disease) study can guide therapy adjustments or preemptive interventions that might avoid hematological relapse. METHODS: Clinical decision making and patient outcome were evaluated in 80 real-life childhood ALL patients, according to the results observed in 544 bone marrow samples analyzed with three MRD methods: multiparametric flow cytometry (MFC), fluorescent in-situ hybridization (FISH) on B or T-purified lymphocytes and patient-specific nested reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Estimated 5 year overall survival and event-free survival were 94% and 84.1%, respectively. A total of 12 relapses in 7 patients were associated with positive MRD detection with at least one of the three methods: MFC (p < 0.00001), FISH (p < 0.00001) and RT-PCR (p = 0.013). MRD assessment allowed the anticipation of relapse and adapted early interventions with different approaches including chemotherapy intensification, blinatumomab, HSCT and targeted therapy to halt relapse in five patients, although two of them relapsed afterwards. CONCLUSION: MFC, FISH and RT-PCR are complementary methods for MRD monitoring in pediatric ALL. Although, our data clearly show that MDR positive detection is associated with relapse, continuation of standard treatment, intensification or other early interventions were able to halt relapse in patients with different risks and genetic background. More sensitive and specific methods are warranted to enhance this approach. However, whether early treatment of MRD can improve overall survival in patients with childhood ALL needs to be evaluated in adequately controlled clinical trials.

Protective Efficacy of a Mucosal Influenza Vaccine Formulation Based on the Recombinant Nucleoprotein Co-Administered with a TLR2/6 Agonist BPPcysMPEG.

Current influenza vaccines target highly variable surface glycoproteins; thus, mismatches between vaccine strains and circulating strains often diminish vaccine protection. For this reason, there is still a critical need to develop effective influenza vaccines able to protect also against the drift and shift of different variants of influenza viruses. It has been demonstrated that influenza nucleoprotein (NP) is a strong candidate for a universal vaccine, which contributes to providing cross-protection in animal models. In this study, we developed an adjuvanted mucosal vaccine using the recombinant NP (rNP) and the TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl-poly-ethylene-glycol (BPPcysMPEG). The vaccine efficacy was compared with that observed following parenteral vaccination of mice with the same formulation. Mice vaccinated with 2 doses of rNP alone or co-administered with BPPcysMPEG by the intranasal (i.n.) route showed enhanced antigen-specific humoral and cellular responses. Moreover, NP-specific humoral immune responses, characterized by significant NP-specific IgG and IgG subclass titers in sera and NP-specific IgA titers in mucosal territories, were remarkably increased in mice vaccinated with the adjuvanted formulation as compared with those of the non-adjuvanted vaccination group. The addition of BPPcysMPEG also improved NP-specific cellular responses in vaccinated mice, characterized by robust lymphoproliferation and mixed Th1/Th2/Th17 immune profiles. Finally, it is notable that the immune responses elicited by the novel formulation administered by the i.n. route were able to confer protection against the influenza H1N1 A/Puerto Rico/8/1934 virus.

Receptor-binding domain-based SARS-CoV-2 vaccine adjuvanted with cyclic di-adenosine monophosphate enhances humoral and cellular immunity in mice.

Novel adjuvants are highly desired to improve immune responses of SARS-CoV-2 vaccines. This work reports the potential of the stimulator of interferon genes (STING) agonist adjuvant, the cyclic di-adenosine monophosphate (c-di-AMP), in a SARS-CoV-2 vaccine based on the receptor binding domain (RBD). Here, mice immunized with two doses of monomeric RBD adjuvanted with c-di-AMP intramuscularly were found to exhibit stronger immune responses compared to mice vaccinated with RBD adjuvanted with aluminum hydroxide (Al(OH)3 ) or without adjuvant. After two immunizations, consistent enhancements in the magnitude of RBD-specific immunoglobulin G (IgG) antibody response were observed by RBD + c-di-AMP (mean: 15360) compared to RBD + Al(OH)3 (mean: 3280) and RBD alone (n.d.). Analysis of IgG subtypes indicated a predominantly Th1-biased immune response (IgG2c, mean: 14480; IgG2b, mean: 1040, IgG1, mean: 470) in mice vaccinated with RBD + c-di-AMP compared to a Th2-biased response in those vaccinated with RBD + Al(OH)3 (IgG2c, mean: 60; IgG2b: n.d.; IgG1, mean: 16660). In addition, the RBD + c-di-AMP group showed better neutralizing antibody responses as determined by pseudovirus neutralization assay and by plaque reduction neutralization assay with SARS-CoV-2 wild type. Moreover, the RBD + c-di-AMP vaccine promoted interferon-γ secretion of spleen cell cultures after RBD stimulation. Furthermore, evaluation of IgG-antibody titers in aged mice showed that di-AMP was able to improve RBD-immunogenicity at old age after 3 doses (mean: 4000). These data suggest that c-di-AMP improves immune responses of a SARS-CoV-2 vaccine based on RBD, and would be considered a promising option for future COVID-19 vaccines.

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia.

PURPOSE: Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. METHODS: In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). RESULTS: Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. CONCLUSIONS: MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.

Identification of Immunodominant Antigens From a First-Generation Vaccine Against Cutaneous Leishmaniasis.

Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the Leishmania genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against L. amazonensis and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total L. amazonensis antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 104 infective parasites of L. amazonensis on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of L. amazonensis were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the Leishmania genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis.

Evaluation of an educational intervention (edworkcases) involving clinical cases and Nursing students: a cross-sectional observational study.

OBJECTIVE: to evaluate the impact of the (edworkcases) educational intervention on students' evaluation outcomes in their clinical practices, their attitudes towards Nursing diagnoses, and their satisfaction. METHOD: this study used a cross-sectional observational design. The participants were 69 third-year Nursing students from a public university in Madrid, Spain. The data analysed in the study were the grades obtained by students for their clinical practices, as well as pre-post intervention scores on the Positions on Nursing Diagnosis Scale and a satisfaction survey. A means comparison by participation in the project (yes/no) was carried out using Student's t-test. A means comparison by professor was conducted using Kruskal-Wallis tests. RESULTS: participation rate: 72.4%; 92% of the participants were women; median age = 21 years old. Statistically significant differences were found between participants and non-participants in terms of mean score in the Overall Evaluation and in the Case Study Evaluation, with higher scores found among the group of participants. The mean score for attitudes towards Nursing diagnoses was 99.9 (SD=2.8) before the intervention and 111.1 (SD=2.9) after the intervention [95% CI: 3.3-19.2]. CONCLUSION: the use of (edworkcases) as part of the practical training was considered satisfactory, enabling theory and practice to be combined and improving students' attitudes towards Nursing diagnoses.

Evaluation of an educational intervention (edworkcases) involving clinical cases and Nursing students: a cross-sectional observational study / Avaliação de uma intervenção educacional (edworkcases) envolvendo casos clínicos e estudantes de Enfermagem: um estudo observacional transversal / Evaluación de una intervención educativa (edworkcases) que involucra casos clínicos y estudiantes de Enfermería: estudio transversal y observacional

Abstract Objective: to evaluate the impact of the (edworkcases) educational intervention on students' evaluation outcomes in their clinical practices, their attitudes towards Nursing diagnoses, and their satisfaction. Method: this study used a cross-sectional observational design. The participants were 69 third-year Nursing students from a public university in Madrid, Spain. The data analysed in the study were the grades obtained by students for their clinical practices, as well as pre-post intervention scores on the Positions on Nursing Diagnosis Scale and a satisfaction survey. A means comparison by participation in the project (yes/no) was carried out using Student's t-test. A means comparison by professor was conducted using Kruskal-Wallis tests. Results: participation rate: 72.4%; 92% of the participants were women; median age = 21 years old. Statistically significant differences were found between participants and non-participants in terms of mean score in the Overall Evaluation and in the Case Study Evaluation, with higher scores found among the group of participants. The mean score for attitudes towards Nursing diagnoses was 99.9 (SD=2.8) before the intervention and 111.1 (SD=2.9) after the intervention [95% CI: 3.3-19.2]. Conclusion: the use of (edworkcases) as part of the practical training was considered satisfactory, enabling theory and practice to be combined and improving students' attitudes towards Nursing diagnoses.

Resumo Objetivo: avaliar o impacto da intervenção educacional (edworkcases) nos resultados da avaliação dos alunos em suas práticas clínicas, suas atitudes em relação aos diagnósticos de Enfermagem e sua satisfação. Método: estudo observacional transversal, realizado com 69 estudantes do terceiro ano de Enfermagem de uma universidade pública de Madri, Espanha. Os dados analisados foram obtidos das notas dos alunos em suas práticas clínicas, bem como, os escores pré- e pós-intervenção na Escala de Posições frente ao Diagnóstico de Enfermagem e uma pesquisa de satisfação. A comparação de médias por participação no projeto (sim/não) foi realizada por meio do teste t de Student. A comparação de médias por professor foi realizada por meio de testes de Kruskal-Wallis. Resultados: taxa de participação: 72,4%; 92% dos participantes eram mulheres; mediana de idade de 21 anos. Foram encontradas diferenças estatisticamente significativas entre participantes e não participantes em termos de pontuação média na Avaliação Geral e na Avaliação do Estudo de Caso, com maiores pontuações encontradas entre o grupo de participantes. A pontuação média das atitudes em relação aos diagnósticos de Enfermagem foi de 99,9 (DP=2,8) antes da intervenção e 111,1 (DP=2,9) após a intervenção [IC 95%: 3,3-19,2]. Conclusão: a utilização de edworkcases como parte do treinamento prático foi considerada satisfatória, permitindo a articulação teoria e prática e melhorando as atitudes dos alunos em relação aos diagnósticos de Enfermagem.

Resumen Objetivo: evaluar el efecto de la intervención educativa (edworkcases) sobre los resultados de la evaluación de los estudiantes en sus prácticas clínicas, sus actitudes hacia los diagnósticos de Enfermería y su nivel de satisfacción. Método: en este estudio se empleó un diseño transversal y observacional. Los participantes fueron 68 estudiantes de tercer año de la carrera de Enfermería de una universidad pública de Madrid, España. Los datos que se analizaron en el estudio fueron las calificaciones obtenidas por los estudiantes en sus prácticas clínicas, al igual que las puntuaciones antes y después de la intervención en la Escala de Posicionamiento ante el Diagnóstico de Enfermería y en una encuesta de satisfacción. Se utilizó la prueba t de Student para realizar una comparación de valores medios por participación en el proyecto (sí/no). La comparación de valores medios por profesor se llevó a cabo por medio de pruebas Kruskal-Wallis. Resultados: índice de participación: 72,4%; el 92% de los participantes eran mujeres, con una mediana de edad de 21 años. Se encontraron diferencias estadísticamente significativas entre participantes y no participantes en cuanto a la puntuación media en la Evaluación General y en la Evaluación de Estudios de Caso, con puntuaciones más elevadas en el grupo de participantes. Las puntuaciones medias correspondientes a las actitudes con respecto a los diagnósticos de Enfermería fueron 99,9 (SD=2,8) y 111.1 (SD=2.9) antes y después de la intervención, respectivamente [IC 95%: 3,3-19,2]. Conclusión: se consideró satisfactorio utilizar edworkcases como parte te la capacitación práctica, lo que permitió combinar teoría y práctica y mejorar las actitudes de los estudiantes con respecto a los diagnósticos de Enfermería.

Identification of immunodominant antigens from a first-generation vaccine against cutaneous Leishmaniasis

Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the Leishmania genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against L. amazonensis and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total L. amazonensis antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 104 infective parasites of L. amazonensis on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of L. amazonensis were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the Leishmania genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis.

International psychometric validation of the Living with Chronic Illness Scale in Spanish-speaking patients with chronic obstructive pulmonary disease.

OBJECTIVES: To validate the Living with Chronic Illness (LW-CI) Scale in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational, cross-sectional validation study with retest. Acceptability, reliability, precision and construct validity were tested. SETTING: The study took place in primary and secondary specialised units of public and private hospitals of Spain and Colombia. PARTICIPANTS: The study included 612 patients with COPD assessed from May 2018 to May 2019. A consecutive cases sampling was done. Inclusion criteria included: (A) patients with a diagnosis of COPD; (B) native Spanish speaking; (C) able to read and understand questionnaires; and (D) able to provide informed consent. Exclusion criteria included: (A) cognitive deterioration and (B) pharmacological effect or disorder that could disrupt the assessment. RESULTS: The LW-CI-COPD presented satisfactory data quality, with no missing data or floor/ceiling effects, showing high internal consistency for all the domains (Cronbach's alpha for the total score 0.92). Test-retest reliability was satisfactory (intraclass correlation coefficient=0.92). The LW-CI-COPD correlated 0.52-0.64 with quality of life and social support measures. The scale demonstrated satisfactory known-groups validity, yielding significantly different scores in patients grouped according to COPD severity levels. CONCLUSIONS: This has been the first validation study of the LW-CI-COPD. It is a feasible, reliable, valid and precise self-reported scale to measure living with COPD in the Spanish-speaking population. Therefore, it could be recommended for research and clinical practice to measure this concept and evaluate the impact of centred-care interdisciplinary interventions based on the patients' perspective, focused on providing holistic and comprehensive care to patients with COPD.

Psychometric Validation of the Living with Chronic Illness Scale in Patients with Chronic Heart Failure.

It is necessary to develop self-reported instruments that evaluate the process of living with chronic heart failure (HF) holistically. The Living with Chronic Illness Scale-HF (LW-CI-HF) is the only available tool to evaluate how patients are living with HF. The aim is to analyse the psychometric properties of the LW-CI scale in the HF population. An international, cross-sectional validation study was carried out in 603 patients living with HF from Spain and Colombia. The variables measured were living with HF, perceived social support, satisfaction with life, quality of life and global impression of severity. The LW-CI-HF scale presented good data quality and acceptability. All domains showed high internal consistency with Cronbach's alpha coefficient ≥ 0.7. The intraclass correlation coefficient for the total score was satisfactory (0.9) in test-retest reliability. The LW-CI-HF correlated 0.7 with social support and quality of life measures. Standard error of measurement was 6.5 for total scale. The LW-CI-HF scale is feasible, reliable and valid. However, results should be taken with caution in order to be used in clinical practice to evaluate the complex process of living with HF. Further research is proposed.

Análisis de la investigación mundial sobre vacunas conjugadas con la plataforma BD-BiPat / Analysis of the global research on conjugate vaccines with the BD-BiPat platform

La tecnología para el desarrollo de vacunas conjugadas preventivas consiste en la unión de polisacáridos bacterianos y una proteína portadora. Este procedimiento constituye uno de los principales desafíos en el mundo de la vacunología y por tanto del Comité Nacional de Expertos en Vacunas. Este órgano, guía y discute las estrategias para el desarrollo e introducción de nuevas vacunas en Cuba. El objetivo de este trabajo fue realizar un análisis de la investigación mundial sobre vacunas conjugadas con la plataforma BD-BiPat (Instituto Finlay de Vacunas, Cuba). La plataforma BD-BiPat permite acceder con formularios de búsqueda directamente a los MeSH a través de PubMed y extraer los datos para su normalización, análisis y visualización. El término usado fue Vaccines, Conjugate. El corpus de datos constó de 3852 registros a los que se aplicaron indicadores métricos de co-ocurrencia y visualizaciones en forma de redes. Los resultados del estudio permitieron evidenciar que es una tecnología muy efectiva, que se ha incrementado rápidamente a nivel mundial. Entre los agentes infecciosos asociados a vacunas conjugadas más estudiados están: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae y Salmonella Typhi. Estados Unidos de América y Reino Unido fueron los países más productivos. Los resultados obtenidos podrían tributar a los decisores en política científica de instituciones dedicadas al desarrollo de vacunas, así como su introducción en programas de vacunación. Igualmente, las funcionalidades de la aplicación web BD-BiPat pueden extenderse a los grupos de vigilancia e inteligencia del sector(AU)

The technology for the development of conjugate vaccines consist of the union of bacterial polysaccharides and a protein carrier. This procedure constitutes one of the main challenges in the world of vaccinology and therefore of the Cuban Expert Committee on Vaccines. This committee guides and discusses strategies for the development and introduction of new vaccines in Cuba. The aim of this work was to perform an analysis of the global research on conjugated vaccines with the BD-BiPat platform (Finlay Institute of Vaccines, Cuba). This platform allows access with search forms directly to the PubMed MeSH and extract data for normalization, analysis and visualization. The term used was Vaccines, Conjugate. The data corpus consisted of 3852 records to which metric indicators of co-occurrence and visualizations in the form of networks were applied. The study showed that it is a novel technology, which has increased rapidly worldwide. Among the most studied infectious agents associated with conjugate vaccines are Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Salmonella Typhi. The United States of America and the United Kingdom were the most productive countries. Results could be useful for decision-makers in scientific policy for the vaccine development, as well as introduction of vaccines in programs of immunization. Likewise, the functionalities of the BD-BiPat platform can be extended to surveillance and intelligence groups in this sector(AU)

Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis.

BACKGROUND Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.

Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis

BACKGROUND Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.

Análise da ética de princípios, 40 anos depois / An analysis of the ethics of principles, 40 years later / Análisis de la ética de principios, 40 años después

Resumen La Bioética de principios se ha convertido en un paradigma de la valoración moral en la práctica clínica. La estructuración en cuatro principios (autonomía, beneficencia, no maleficencia y justicia), elaborada por Beauchamp y Childress hace casi 40 años, trata de facilitar la toma de decisiones en un contexto universal. Aun así, este objetivo genera una serie de dudas que afectan profundamente a la praxis ética de la medicina y a la teoría moral. Por ello, se hace imprescindible un análisis crítico de los principios de la Bioética, su fundamentación teórica y su aplicabilidad, a la vista de los resultados en estos últimos decenios.

Abstract Bioethics of principles has become a paradigm of moral evaluation in clinical practice. This model is based on four principles (autonomy, beneficence, non-maleficence and justice), as defined by Beauchamp and Childress almost 40 years ago. The four principles try to facilitate decision-making in a universal context. However, this objective generates a series of questions that deeply affect the ethical practice of medicine and the moral theory. Therefore, a critical analysis of the bioethical principles, its theoretical foundation and its application, in view of the results in recent decades, is needed.

Resumo A Bioética dos princípios tornou-se paradigma de avaliação moral na prática clínica. A estruturação desse modelo em quatro princípios (autonomia, beneficência, não maleficência e justiça), desenvolvidos por Beauchamp e Childress há quase 40 anos, visa facilitar a tomada de decisão em contexto universal. No entanto, esse objetivo gera uma série de questões que afetam profundamente a prática ética da medicina e a teoria moral. Por essa razão, a análise crítica dos princípios da Bioética, sua fundamentação teórica e sua aplicabilidade, levando em consideração os resultados das últimas décadas, são essenciais.

Requerimientos para mejorar la normalización de datos en software de análisis métricos de la información / Requirements to improve the normalization of data in software for metric analysis of information

Por la diversidad de formas en la entrada de los campos de autor-afiliación, la normalización de los datos bibliográficos es uno de los problemas que limitan los análisis de información métrica en tiempo de ejecución, fiabilidad de los indicadores y tamaño del corpus de datos. Este trabajo tiene como objetivo proponer los requerimientos para el mejoramiento de la normalización de datos en software de análisis métricos. Para lograr el objetivo se realizó un diagnóstico de los principales métodos y técnicas que son empleados a nivel mundial en este tipo de estudio. Como resultado principal, se relacionan los requerimientos para una aplicación de preprocesamiento automatizado de datos con fines métricos. Se proponen la base de datos, las tareas, los pasos y los algoritmos que contendrá esa aplicación. Se debe usar una combinación de algoritmos para desambiguar los campos afiliación y autor(AU)

Due to the diversity of methods used to enter author-affiliation information, the resulting lack of standardization of bibliographic data has become one of the problems limiting analysis of metric information in terms of execution time, reliability of indicators and size of the data corpus. The purpose of the study was to propose requirements to improve data normalization in metric analysis software. To achieve this objective, a diagnosis was made of the main methods and techniques used worldwide in this type of study. The main result is the presentation of requirements to be met by an application for automated pre-processing of data for metric purposes. A proposal is made of the database, tasks, steps and algorithms that this application will contain. A combination of algorithms should be used to disambiguate author and affiliation fields(AU)

Tuberculosis, Bacillus Calmette-Guérin (BCG) y vacunas de tuberculosis: análisis de patentes / Tuberculosis, Bacillus Calmette-Guérin (BCG) and tuberculosis vaccines: a patent analysis

La relación de la tuberculosis, el Bacillus Calmette-Guérin y las vacunas de tuberculosis como dominio bajo estudio, parte del hecho de que la única vacuna disponible hoy para prevenir la tuberculosis en humanos es la BCG, y el mejoramiento de ella o el desarrollo de nuevas vacunas es estratégico para el control de esta enfermedad. Este estudio pretende contribuir con estas importantes investigaciones a partir de los estudios patentométricos, y tiene como objetivo realizar un análisis métrico que permita describir la productividad de patentes sobre tuberculosis, Bacillus Calmette-Guérin y vacunas de tuberculosis en un determinado periodo de tiempo. Para el estudio de la productividad se analizó el comportamiento de indicadores temporales y geográficos en el dominio, en el que se utilizaron técnicas y herramientas apropiadas para los documentos de patentes. A la investigación de la tuberculosis como enfermedad infecciosa transmisible se le han dedicado grandes esfuerzos. La tuberculosis fue considerada hasta hace poco un problema de salud de los países en desarrollo, mientras hoy, con la reemergencia de la enfermedad, los países desarrollados han acaparado su investigación; sin embargo, estos esfuerzos no han sido proporcionales con la investigación dedicada a una nueva generación de vacunas contra esta enfermedad y no existen nuevas patentes que lo demuestren...

As an object of study, the relationship between tuberculosis, Bacillus Calmette-Guérin and tuberculosis vaccines starts from the fact that the only vaccine currently available to prevent tuberculosis in humans is BCG, and its improvement or the development of new vaccines is a key strategy to control the disease. The present study intends to make a contribution to such important research from a patent metrics perspective. Its purpose is to conduct a metric analysis allowing to describe the productivity of patents for tuberculosis, Bacillus Calmette-Guérin and tuberculosis vaccines in a given time period. For the productivity study, an analysis was carried out of the behavior of temporal and geographic indicators in the domain, using techniques and tools suitable for patent documents. Research into tuberculosis as an infectious communicable disease has received great attention. Until recently, tuberculosis was considered to be a health problem in the developing world. However, after its re-emergence, research has been mainly conducted in developed countries. But such efforts have not been in proportion to research aimed at developing a new generation of vaccines against the disease, and there are no new patents supporting them...

Development of a universal CTL-based vaccine for influenza.

In pursuit of better influenza vaccines, many strategies are being studied worldwide. An attractive alternative is the generation of a broadly cross-reactive vaccine based on the induction of cytotoxic T-lymphocytes (CTL) directed against conserved internal antigens of influenza A virus. The feasibility of this approach using recombinant viral vectors has recently been demonstrated in mice and humans by several research groups. However, similar results might also be achieved through immunization with viral proteins expressed in a prokaryotic system formulated with the appropriate adjuvants and delivery systems. This approach would be much simpler and less expensive. Recent results from several laboratories seem to confirm this is as a valid option to be considered.

La investigación en Cuba sobre evaluación de bibliotecas / The investigation in Cuba about libraries evaluation

Hay varias razones por las que es importante para las bibliotecas evaluar los procesos de sus organizaciones, los recursos y servicios. Conocer el estado del arte en un tema es parte del caudal del conocimiento que sobre la disciplina debe dominar un profesional de la información. Por eso, este trabajo se ha trazado como objetivo revisar y analizar la investigación en Cuba sobre evaluación de bibliotecas. Para lograrlo fue necesario crear una base de datos a partir de diversas fuentes como los trabajos presentados en los Congresos INFO´s y los publicados en la revista Acimed. Los resultados han permitido identificar las características de la evaluación bibliotecaria en Cuba y su comportamiento por tipos de bibliotecas. Se define, además, la evaluación bibliotecaria como un proceso integrador, vinculado a la gestión de la calidad y se plantean una serie de consideraciones sobre las contribuciones hechas en Cuba sobre el tema

There are several important reasons for the libraries to evaluate the processes of their organizations, the resources and services. To know the state of the art in a topic, it is part of the flow of the knowledge that it has more than enough of the discipline, a professional of the information it should dominate. For that reason, this paper aim was to analyze the investigation about libraries evaluation in Cuba. For it was necessary to create a database (BD) starting from diverse sources like the papers presented in the Congresses INFO´s and in the magazine ACIMED. The results have allowed us to identify the characteristics of the librarian evaluation in Cuba and the indicators used to make the evaluation in different kinds of libraries. Is defined, also, the librarian evaluation like an integrative process, linked to the management of the quality and bring up a series of considerations on the parts made in Cuba on the subject

Aproximaciones a la visibilidad de la ciencia y la producción científica de Cuba en el sector de la salud / Approaches to visibility of science and scientific production of Cuba in the health area

Con el objetivo de caracterizar la producción científica generada en el área de la salud en Cuba, fundamentalmente desde la perspectiva de su visibilidad, se analizó una serie de estudios métricos realizados por el Centro Nacional de Información de Ciencias Médicas-Infomed sobre este tema. Se analiza la importancia del procesamiento de la producción científica de Cuba en las grandes bases de datos para obtener una alta visibilidad internacional. Finalmente, se estudiaron los aportes y principales limitaciones de los estudios sobre producción científica desarrollados por el Centro Nacional de Información de Ciencias Médicas-Infomed.

With the aim to characterize the scientific production in the health sciences area in Cuba, we analyzed a group of metric studies make by National Center of Health Sciences Information-Infomed on this topic. The importance of the process of Cuban scientific production in the largest database to obtain high international visibility is analyzed. Finally, were studied the contributions and main limitations of the previous studied about scientific production developed by the National Center of Health Sciences information-Infomed.